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Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection
Gut Microbes ( IF 12.2 ) Pub Date : 2022-08-01 , DOI: 10.1080/19490976.2022.2105609
Julia A Brown 1, 2 , Katherine Z Sanidad 1, 2 , Serena Lucotti 1, 2 , Carolin M Lieber 3 , Robert M Cox 3 , Aparna Ananthanarayanan 1, 2 , Srijani Basu 4 , Justin Chen 1 , Mengrou Shan 5 , Mohammed Amir 1, 2 , Fabian Schmidt 6 , Yiska Weisblum 6 , Michele Cioffi 1, 2 , Tingting Li 7 , Florencia Madorsky Rowdo 8 , M Laura Martin 8 , Chun-Jun Guo 7 , Costas Lyssiotis 4 , Brian T Layden 9, 10 , Andrew J Dannenberg 4 , Paul D Bieniasz 6, 11 , Benhur Lee 12 , Naohiro Inohara 5 , Irina Matei 1, 2 , Richard K Plemper 3 , Melody Y Zeng 1, 2
Affiliation  

ABSTRACT

The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple pathways by which the gut microbiome protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity via GPR41 and 43 in male animals. We further identify a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria to dampen viral entry and hypercoagulation and promote adaptive antiviral immunity.



中文翻译:

肠道微生物群衍生的代谢物可预防 SARS-CoV-2 感染

摘要

肠道微生物组与免疫调节和新陈代谢错综复杂,但其在 2019 年冠状病毒病 (COVID-19) 中的作用尚不完全清楚。严重和致命的 COVID-19 的特点是抗病毒免疫力差和高凝状态,特别是在男性中。在这里,我们定义了多种途径,肠道微生物组通过产生短链脂肪酸 (SCFA) 来保护哺乳动物宿主免受 SARS-CoV-2 鼻内感染,包括局部和全身性感染。SCFAs 通过下调 SARS-CoV-2 进入受体、血管紧张素转换酶 2 (ACE2) 并通过 GPR41 和 43 增强雄性动物的适应性免疫,从而降低了气道和肠道中的病毒负荷。我们进一步确定了肠道微生物组通过 Sh2b3-Mpl 轴限制巨核细胞增殖和血小板更新来调节全身凝血反应的新作用。总之,我们的研究结果揭示了 SCFA 和纤维发酵肠道细菌的新功能,以抑制病毒进入和高凝状态并促进适应性抗病毒免疫。

更新日期:2022-08-02
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